Hemophilia APhase 2/3NCT00306670
Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Acquired Hemophilia A
A Phase 2/3 study testing Rituxan and prednisone in people with Hemophilia A, run by Georgetown University.
Trial summary
The purpose of this study is to evaluate the rate of response when administering rituximab to suppress or eliminate the anti-body in a patient's blood that inhibits the effectiveness of their factor replacement product compared to treatment using cyclophosphamide. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Rituxan and prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- No sites listed yet
- Study dates
- Apr 2006to Aug 2011
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Diagnosis of acquired hemophilia A in a previously non-coagulopathic individual.
- Prior treatment with at least 3 weeks of immunosuppressive therapy
- Factor VIII: C levels <50% within 14 days prior to study entry, which do not correct in coagulation assays in which normal plasma is mixed and incubated with patient plasma.
- Measurable anti-factor VIII:C antibody inhibitor activity > 0.6 Bethesda Units/ml.
- Age ³18 years
- Written informed consent
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- Use of an effective means to avoid pregnancy, including abstinence, for women of childbearing potential,.
- Serum bilirubin less than or equal to the upper limit of normal (ULN); ALT and AST £2.5´ ULN within 14 days prior to study entry
- Serum creatinine £1.5´ the ULN within 14 days prior to study entry
- Negative serum pregnancy test, for all women of childbearing potential, within 14 days prior to study entry
Who cannot join
- Continued treatment requirement of prednisone ≥30mg/day or equivalent dosing of other corticosteroid preparations to control serious symptoms of an underlying autoimmune disease state.
- Treatment with cyclophosphamide, danazol, vinca alkaloids, azathioprine, IVIG, or other immunosuppressive, immunomodulatory, or cytotoxic agents (other than decreasing doses of corticosteroids) within 30 days prior to study entry.
- Anticipated need for repeated extracorporeal plasmapheresis in order to reverse refractory bleeding associated with acquired hemophilia.
- Treatment with other experimental agents within 30 days prior to study entry
- Known sensitivity to murine or chimeric products
- Hepatitis BsAg positivity or high risk for reactivation of Hepatitis B.
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- Active infection requiring antibiotic therapy within 7 days prior to study entry
- Current use of any required medications, which in the opinion of the treating physician, could be inducing the formation of auto-FVIII:C inhibitory antibodies
- Prior treatment with rituximab or other monoclonal antibody therapy
- Known HIV antibody positivity
- NCI-CTC Grade ³1 cardiac arrhythmia ( refer to CTC v3)
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
- Currently pregnant women, lactating women, or women within 12 months of delivery, spontaneous miscarriage, or therapeutic or elective termination of pregnancy.
- Known severe leucopenia (absolute neutrophil count <1000/µL) or thrombocytopenia (<25,000/µL);
- Known pre-existing cystitis or severe urinary outflow obstruction.
- Known history of recurrent severe opportunistic infections, eg. generalized herpes zoster;
- Inability or unwillingness to comply with study design and requirements and follow-up procedures.
About this study
Official title: A Prospective, Phase II/III Randomized, Mult-institutional Controlled, Open-label, Phase II Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Patients With Acquired Hemophilia A
The purpose of this study is to evaluate the rate of response when administering rituximab to suppress or eliminate the anti-body in a patient's blood that inhibits the effectiveness of their factor replacement product compared to treatment using cyclophosphamide. This is a Phase 2/3 study to find out what effects (good and bad) and response rituximab has on a patient and their anti-Factor VIII antibodies. Also, to compare the effect (good and bad) of the rituximab with cyclophosphamide on a patient and their anti-Factor VIII antibodies to see which is better. This research is being done because we do not know which treatment regimen (rituximab or cyclophosphamide) is more effective in eliminating or suppressing the anti-Factor VIII antibody in patients with acquired Hemophilia A.
Read the detailed description
This is a prospective Phase II randomized multi-institutional controlled pilot trial comparing the regimen of single agent rituximab with 6 weeks cytotoxic therapy with oral cyclophosphamide to eradicate or suppress autoimmune anti-factor VIII antibodies in individuals with acquired hemophilia A. Patients will be randomized to receive either of these two regimens when their autoimmune anti-factor VIII antibodies prove to be refractory to initial upfront immunosuppressive treatment with oral prednisone 1 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks. Patients will be randomized to the treatment cohorts according to the biostatistical methods.
- Conditions
- Hemophilia A
- Being tested
- Rituxan, prednisone
- Keywords
- Acquired Hemophilia A, Anti-Factor VIII antibodies, Anti-Factor VIII inhibitors, Hemophilia A, Factor VIII inhibitors
- Medical subject headings
- Hemophilia A, Factor 8 deficiency, acquired
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RituxanDrug
Also called Rituximab
Acquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies
prednisoneDrug
Also called corticosteroids
<30 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Rituximab | Experimental | Patients will receive rituximab. Receives: Drug: Rituxan; Drug: prednisone |
| Oral cyclophosphamide | Active comparator | Patients will receive oral cyclophosphamide. Receives: Drug: prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Evaluate the Total Number of Circulating Lymphocytes and Lymphocyte Phenotypes and to Correlate With the Effectiveness of Rituximab and Oral Cyclophosphamide to Achieve and Preserve Complete Eradication of the Refractory Autoantibody.
the 2 recruited patients did not eradicate their inhibitors with 3 weeks of corticosteroids and did not progress in clinical trial since funding was eliminated and study terminated
Measured: When 25 patients have completed the study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Mar 2006 (estimated)
- Study startApr 2006
- Primary completionJan 2011
- Study completionAug 2011
Why it stopped: Sponsor no longer funding study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by Georgetown UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Georgetown University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Craig Kessler, Georgetown University
- Investigators
- Craig Kessler, MD, Principal investigator, Georgetown University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00306670
- Sponsor's protocol ID
- U2688
- Status last verified
- Dec 2016
- First submitted
- 23 Mar 2006
- Last updated
- 10 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective, Phase II/III Randomized, Mult-institutional Controlled, Open-label, Phase II Trial of Rituximab Versus Oral Cyclophosphamide to Eradicate or Suppress Autoimmune Anti-Factor VIII Antibodies in Patients With Acquired Hemophilia A
- ClinicalTrials.gov ID
- NCT00306670
- Acronym / sponsor ID
- U2688
- Conditions
- Hemophilia A
- Keywords
- Acquired Hemophilia A, Anti-Factor VIII antibodies, Anti-Factor VIII inhibitors, Hemophilia A, Factor VIII inhibitors
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor no longer funding study.
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Georgetown UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Apr 2006
- Primary completion
- Jan 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 24 Mar 2006 (estimated)
- Results
- Posted 10 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the rate of response when administering rituximab to suppress or eliminate the anti-body in a patient's blood that inhibits the effectiveness of their factor replacement product compared to treatment using cyclophosphamide. This is a Phase 2/3 study to find out what effects (good and bad) and response rituximab has on a patient and their anti-Factor VIII antibodies. Also, to compare the effect (good and bad) of the rituximab with cyclophosphamide on a patient and their anti-Factor VIII antibodies to see which is better. This research is being done because we do not know which treatment regimen (rituximab or cyclophosphamide) is more effective in eliminating or suppressing the anti-Factor VIII antibody in patients with acquired Hemophilia A.
Detailed description
This is a prospective Phase II randomized multi-institutional controlled pilot trial comparing the regimen of single agent rituximab with 6 weeks cytotoxic therapy with oral cyclophosphamide to eradicate or suppress autoimmune anti-factor VIII antibodies in individuals with acquired hemophilia A. Patients will be randomized to receive either of these two regimens when their autoimmune anti-factor VIII antibodies prove to be refractory to initial upfront immunosuppressive treatment with oral prednisone 1 mg/kg/day (or equivalent corticosteroid doses) for 3 weeks. Patients will be randomized to the treatment cohorts according to the biostatistical methods.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Rituximab | Experimental | Drug: Rituxan, Drug: prednisonePatients will receive rituximab. |
| Oral cyclophosphamide | Active comparator | Drug: prednisonePatients will receive oral cyclophosphamide. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Diagnosis of acquired hemophilia A in a previously non-coagulopathic individual.
- Prior treatment with at least 3 weeks of immunosuppressive therapy
- Factor VIII: C levels <50% within 14 days prior to study entry, which do not correct in coagulation assays in which normal plasma is mixed and incubated with patient plasma.
- Measurable anti-factor VIII:C antibody inhibitor activity > 0.6 Bethesda Units/ml.
- Age ³18 years
Key exclusion criteria (17 listed)
- Continued treatment requirement of prednisone ≥30mg/day or equivalent dosing of other corticosteroid preparations to control serious symptoms of an underlying autoimmune disease state.
- Treatment with cyclophosphamide, danazol, vinca alkaloids, azathioprine, IVIG, or other immunosuppressive, immunomodulatory, or cytotoxic agents (other than decreasing doses of corticosteroids) within 30 days prior to study entry.
- Anticipated need for repeated extracorporeal plasmapheresis in order to reverse refractory bleeding associated with acquired hemophilia.
- Treatment with other experimental agents within 30 days prior to study entry
- Known sensitivity to murine or chimeric products
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RituxanAlso: RituximabAcquired Hemophilia A Patients Who Have Developed Anti-Factor VIII Antibodies | Drug | Rituximab |
| prednisoneAlso: corticosteroids<30 mg/day | Drug | Oral cyclophosphamide, Rituximab |
Primary outcome
To Evaluate the Total Number of Circulating Lymphocytes and Lymphocyte Phenotypes and to Correlate With the Effectiveness of Rituximab and Oral Cyclophosphamide to Achieve and Preserve Complete Eradication of the Refractory Autoantibody.
Time frame: When 25 patients have completed the study.
the 2 recruited patients did not eradicate their inhibitors with 3 weeks of corticosteroids and did not progress in clinical trial since funding was eliminated and study terminated
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig Kessler, MD principal investigator
Georgetown University Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Rituxan and prednisone in people with Hemophilia A, run by Georgetown University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To Evaluate the Total Number of Circulating Lymphocytes and Lymphocyte Phenotypes and to Correlate With the Effectiveness of Rituximab and Oral Cyclophosphamide to Achieve and Preserve Complete Eradication of the Refractory Autoantibody. (time frame: When 25 patients have completed the study.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2017.